William A. Harris FRS
Professor of Physiology, Development and Neuroscience
Tel:
+44 (0)1223 333772, Fax: +44 (0)1223 333786, E-mail: harris@mole.bio.cam.ac.uk
Molecular Embryogenesis of the Visual System
Where does the nervous system come from in the embryo? How does it grow to the right size and shape? How do stem cells turn into more committed neuronal progenitors and how do these cells know when to leave the cycle and differentiate into neural and glial progenitors? How do particular regions of the nervous system produce the right number of neurons and the right proportions of the different types of neurons? Once born, how do these precursors differentiate? How do they choose a particular cell type to become amongst a myriad of possible fates, and by what cellular mechanisms do these cells become properly polarised, branched, and integrated into the retinal circuitry? What mechanisms allow retinal ganglion cells to send out long axons that forge pathways to their targets in the brain, and recognise specific cells within these targets?
The visual systems of Xenopus and zebrafish are ideal for such questions because of their embryological, molecular and genetic accessibility to experimentation, combined with the possibility of in vivo time-lapse imaging. The retina is an excellent system to explore the issue of cellular proliferation and diversity. We are unravelling some of the lineage dependent and lineage independent events that are used to push or induce cells to transition from proliferating retinal stem cells to differentiated neurons and glia particular fates and testing a variety of hypotheses concerning the mechanisms of fate specification and histogenesis. We are using similar approaches to investigate the mechanisms involved in the initial morphogenesis of various retinal neuron types. We are also conducting a variety of experiments on how the growing axons gather and transduce the information that allows them to find their way to their targets, exploring the machinery and the dynamics of growth cones at a molecular level.
Colleagues:
Dr Xana Almeida (Postdoctoral Fellow)
Dr Je He (Postdoctoral Fellow)
Mr Owen Randlett (Graduate Student)
Miss Rene Chow (Graduate Student)
Miss Nicola Love (Graduate Student)
Main Collaborators:
Christine Holt (PDN)
Richard Adams (PDN)
Anna Philpott (Oncology)
Ben Simons (Physics)
Jochen Guck (Physics)
Roger Pedersen (Surgery)
Dr Muriel Perron (CNRS)
Monica Vetter (University of Utah)
Steve Wilson (Kings College London)
Dr Michalis Agathocleous (Univesity of Michigan)
Dr Caren Norden (MPI Dresden)
Dr Giuseppe Lupo (University of Rome)
Dr Patricia Yap (Monash University)
Lucia Poggi (University of Heidelberg)
Michel Cayouette (IRCM Montreal)
Rachel Wong (University of Washington)
Main sources of funding: Wellcome Trust.
Selected publications:
Randlett O, Norden C, Harris WA. (2011) The vertebrate retina: a model for neuronal polarization in vivo. Dev Neurobiol. 71:567-83
Lupo G, Gestri G, O'Brien M, Denton RM, Chandraratna RA, Ley SV, Harris WA, Wilson SW. (2011) Retinoic acid receptor signaling regulates choroid fissure closure through independent mechanisms in the ventral optic cup and periocular mesenchyme. Proc Natl Acad Sci U S A. 108:8698-703
Randlett O, Poggi L, Zolessi FR, Harris WA. (2011) The oriented emergence of axons from retinal ganglion cells is directed by laminin contact in vivo. Neuron. 70:266-80
Jusuf PR, Almeida AD, Randlett O, Joubin K, Poggi L, Harris WA. (2011) Origin and determination of inhibitory cell lineages in the vertebrate retina. J Neurosci. 31:2549-62
Gomes FL, Zhang G, Carbonell F, Correa JA, Harris WA, Simons BD, Cayouette M. (2011) Reconstruction of rat retinal progenitor cell lineages in vitro reveals a surprising degree of stochasticity in cell fate decisions. Development 138:227-35
Norden C, Young S, Link BA, Harris WA. (2009) Actomyosin is the main driver of interkinetic nuclear migration in the retina. Cell. 138:1195-208
Agathocleous M, Iordanova I, Willardsen MI, Xue XY, Vetter ML, Harris WA, Moore KB. (2009) A directional Wnt/beta-catenin-Sox2-proneural pathway regulates the transition from proliferation to differentiation in the Xenopus retina. Development 136:3289-99
